Any publications or references discussed herein are presented to describe the background of the invention and to provide additional detail regarding its practice. Nothing herein is to be construed as an admission that the inventors are not entitled to antedate such disclosure by virtue of prior invention.
The replacement or repair of damaged or diseased tissues or organs by implantation is a continuing goal of the medical profession. As a part of that work, there is an increasing interest in tissue engineering techniques where biocompatible, biodegradable materials are used as a support matrix or as a substrate for the delivery of therapeutic agents. However, there are a number of difficulties that restrict the use of implanted materials.
One particular class of polymers that have proven useful are hydrogels. Hydrogels are materials consisting of a three-dimensional network of hydrophilic polymers with water filling the space between the polymer chains. Hydrogels may be obtained by copolymerizing suitable hydrophilic monomers, by chain extension, and by cross-linking hydrophilic pre-polymers or polymers.
A thermoreversible hydrogel matrix, which is liquid near physiologic temperatures, has been shown to elicit vasculogenesis and modulate wound healing. This bioactive hydrogel material has also been shown to improve healing in response to implanted foreign materials; demonstrating a decrease in the surrounding fibrous capsule thickness and a persistent increase in blood supply immediately adjacent to implanted materials exposed to this thermoreversible hydrogel. However, that thermoreversible hydrogel is molten at physiologic temperatures, rendering it inappropriate for use in vivo (see WO 2003/072155).
A particular biopolymer for use in medical applications is disclosed in U.S. Pat. No. 6,132,759, which relates to a biopolymer matrix comprising gelatin cross-linked with oxidized polysaccharides. The biopolymer of the '759 patent is said to be useful for treating skin wounds or dermatological disorders when appropriate drugs are incorporated.
U.S. Pat. No. 5,972,385 describes a matrix comprising a modified polysaccharide with collagen for tissue repair, which can be combined with growth factors.
U.S. Pat. No. 6,287,588 describes a matrix comprising a continuous biocompatible gel phase, such as a hydrogel, and a discontinuous particulate phase, such as microspheres, and a therapeutic agent contained in both phases. The '588 patent does not discuss wound sealing or any use in conjunction with an interbody device.
Additional publications and patents have described polymers and co-polymers for use in medical applications, such as drug delivery, tissue regeneration, wound healing, wound dressings, adhesion barriers, and wound adhesives. For example, see U.S. Pat. No. 4,618,490 and U.S. Pat. No. 6,165,488.
A large number of the biocompatible polymers previously known are based at least in part on collagen, collagen derived material, polysaccharides, particularly dextran and cross-linked gelatin and dextran.
In addition, wound sealants known in the art typically rely upon the use of fibrinogen, thromboplastin and/or a clotting factor, for example, see WO 97297972, U.S. Pat. No. 5,219,328, U.S. Pat. No. 5,292,333, U.S. Pat. No. 5,645,849, U.S. Pat. No. 5,643,596, U.S. Pat. No. 6,168,788, U.S. Pat. No. 5,981,621, and U.S. Pat. No. 6,607,631.
In addition, there still remains a need for a hydrogel that is settable when in contact with living tissue and that functions as a wound sealant that fosters tissue growth, and that optionally can effectively deliver a therapeutic agent.